Polymerase proofreading-associated polyposis (PPAP) due to a heritable mutation POLE (p.L424V) or POLD1 (p.S479N) is an autosomal dominant condition.

This risk management guideline has been developed for individuals who have NOT been diagnosed with a relevant cancer/tumour. The care of affected individuals should be individualised based on their clinical situation, and the monitoring they need as part of their treatment and post-treatment follow up.

**increased risk of other tumour types has been suggested (including cancer of the breast, stomach, ovary and brain) but more research is required due to ascertainment bias in these initial studies.rr Screening and advice should therefore be based on the family history of these tumours.

The effectiveness of cancer screening in individuals with POLE and POLD1 mutations are still unclear. Recommendations have been extrapolated from cancer screening studies in other related hereditary cancer syndromes such as Lynch syndrome, MAP and attenuated FAP.

Colorectal cancer

Surgical

Data suggests polyposis may be more severe in POLE mutation carriers.rr For individuals with significant polyps (3 before 30 or >10 lifetime), recommendations are based on MUTYH associated polyposis (MAP) and includes colectomy when polyp burden becomes unmanageable.r

Endometrial cancer

Surgical

Surveillance

There is no evidence to support a survival benefit from transvaginal ultrasound (TVU) and aspiration biopsy. Where possible, surveillance should be offered in the context of a clinical trial.

Duodenum

There are no studies to show the efficacy of gastrointestinal endoscopy in reducing the risk for duodenal cancer. There is an increased risk for duodenal polyps and cancer and surveillance has been recommended on the basis of the similarities of the MUTYH associated polyposis (MAP) phenotype and attenuated familial adenomatous polyposis (FAP).r

First degree (blood) relatives (parents/brothers/sisters/children) are at 50% risk of having inherited the gene mutation/or having the condition. First degree relatives should be referred to a local family cancer clinic.

The information contained in this document is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to care or treatment. Any clinician seeking to apply or consult this document is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au